In vitro and in vivo Enhancement of Bactericidal Activity of Phagocytes against &lt;i&gt;Klebsiella pneumoniae &lt;/i&gt;treated with Subminimal Inhibitory Concentrations of Cefodizime

Nomura, Sadahiro; Nagayama, Ariaki

doi:10.1159/000239341

Cited by 5 publications

(7 citation statements)

References 23 publications

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“…Cefodizime (CEF) is an expanded spectrum cephalosporin that shows good experimental and clinical efficacy against lower respiratory tract infections induced by K. pneumoniae (2,12,31,32). The drug has already been shown to enhance the bactericidal activity of phagocytes against K. pneumoniae in a mouse model of peritonitis (27). This apparent immunoenhancing property resulted from reduction of the thickness of the newly synthesized capsule as bacteria divided and tried to proliferate in the presence of sub-MIC levels of CEF (28).…”

mentioning

confidence: 99%

Influence of Cefodizime on Pulmonary Inflammatory Response to Heat-Killed Klebsiella pneumoniae in Mice

Bergeron

Deslauriers

Ouellet

et al. 1999

Antimicrob Agents Chemother

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Encapsulated Klebsiella pneumoniae strains frequently induce fatal nosocomial pneumonia. Cefodizime (CEF) as an antibiotic is suspected to enhance host resistance against various microbial invasions through interactions with bacteria and host cells. To investigate the influence of CEF on the pulmonary response toKlebsiella that does not merely result from direct bacterial clearance by the drug, we inoculated mice with heat-killed fluorescein isothiocyanate-labeled K. pneumoniae. CEF upregulated (P < 0.01) the earlyKlebsiella-induced secretion of tumor necrosis factor alpha, as well as the number (P < 0.01) and phagocytic efficacy (P < 0.001) of alveolar macrophages. By contrast, the late polymorphonuclear neutrophil recruitment (P < 0.05) and levels of interleukin-1 alpha (IL-1α) (P < 0.05) and IL-6 (P < 0.05) were reduced. The stimulation of an early immune response by CEF followed by late reduction in inflammation may be beneficial against bacterial pneumonia.

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confidence: 99%

Influence of Cefodizime on Pulmonary Inflammatory Response to Heat-Killed Klebsiella pneumoniae in Mice

Bergeron

Deslauriers

Ouellet

et al. 1999

Antimicrob Agents Chemother

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“…Interactions between bacteria, macrophages and antimicrobial drugs have already been investigated with macrophages from cell lines [9][10][11][12][13][14], with human macrophages derived from monocytes [15,16] and in a mouse peritonitis model studying whole cells in a peritoneal wash [19]. In the present study, we decided to use macrophages derived from murine bone marrow (BMDM), which have been validated to possess a stronger capacity for both proliferation and phagocytosis than peritoneal or splenic macrophages [20].…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we decided to use macrophages derived from murine bone marrow (BMDM), which have been validated to possess a stronger capacity for both proliferation and phagocytosis than peritoneal or splenic macrophages [20]. Moreover, contrary to previous in vitro studies in which the supernatant was discarded before exposing macrophages and their intracellular bacteria to drugs [9][10][11][12][13][14][15][16], we considered the dynamics of both intracellular and extracellular bacteria simultaneously over time. Indeed, we assume that these two populations are interrelated and that control of both populations is needed to cure an infection.…”

Section: Discussionmentioning

confidence: 99%

“…As resident macrophages are the key sentinels and orchestrators of the inflammatory response against invading pathogens [8], they are relevant cells for studying their interaction with bacteria and antimicrobial drugs. Studies focusing on this tripartite interaction have already been performed with macrophages derived from cell lines [9][10][11][12][13][14] or with human macrophages derived from monocytes [15,16]. However, all these studies focused mainly on the effects on intracellular bacteria, and the drug effects on extracellular bacteria were always assessed separately in the absence of phagocytes.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic interactions between cephalexin and macrophages on different Staphylococcus aureus inoculum sizes: a tripartite in vitro model

et al. 2021

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Background The bactericidal activity of an antimicrobial drug is generally assessed by in vitro bacterial time-kill experiments which do not include any components of the immune system, even though the innate immunity, the primary host defence, is probably able to kill a large proportion of pathogenic bacteria in immunocompetent patients. We developed an in vitro tripartite model to investigate the joint action of C57Bl/6 murine bone-marrow-derived macrophages and cephalexin on the killing of Staphylococcus aureus. Results By assessing the bactericidal effects on four bacterial inoculum sizes, we showed that macrophages can cooperate with cephalexin on inoculum sizes lower than 106 CFU/mL and conversely, protect S. aureus from cephalexin killing activity at the highest inoculum size. Cell analysis by flow cytometry revealed that macrophages were rapidly overwhelmed when exposed to large inoculums. Increasing the initial inoculum size from 105 to 107 CFU/mL increased macrophage death and decreased their ability to kill bacteria from six hours after exposure to bacteria. The addition of cephalexin at 16-fold MIC to 105 and 106 CFU/mL inoculums allowed the macrophages to survive and to maintain their bactericidal activity as if they were exposed to a small bacterial inoculum. However, with the highest inoculum size of 107 CFU/mL, the final bacterial counts in the supernatant were higher with macrophages plus cephalexin than with cephalexin alone. Conclusions These results suggest that if the bacterial population at the infectious site is low, as potentially encountered in the early stage of infection or at the end of an antimicrobial treatment, the observed cooperation between macrophages and cephalexin could facilitate its control.

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“…The literature contains some information in relation to Klebsiella pneumoniae [8,9], but Escherichia coli (a more frequent cause of infection) has not been investigated. The aim of the present study was to investigate the effects of sub-MICs of cefodizime on host neutrophilic defenses, such as phagocytosis, the intracellular killing of E. coli, and oxidative bursts (chemiluminescence).…”

Section: Introductionmentioning

confidence: 99%

Influence of Sub-Minimum Inhibitory Concentrations of Cefodizime on the Phagocytosis, Intracellular Killing and Oxidative Bursts of Human Polymorphonuclear Leukocytes

Braga

Sasso²,

Mancini³

et al. 1999

Chemotherapy

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It is generally recognized that sub-minimum inhibitory concentrations (sub-MICs) of antibiotics are still capable of interfering with some bacterial virulence parameters, thus facilitating host neutrophilic defenses such as phagocytosis, killing and oxidative bursts. This study investigated the interaction of Escherichia coli with these neutrophilic functions after pretreatment with various sub-MICs of cefodizime. E. coli exposed to 1/2 to 1/8 MICs of cefodizime showed the extensive production of long and very long filaments that interfere with the precise measurement of phagocytic and killing parameters. Our analysis was consequently extended to the activity of 1/16 to 1/64 MICs. The interesting finding was that, although phagocytosis was unaffected, killing was significantly increased in one strain at 1/16 MIC and in another at 1/32 MIC while in the last strain it was unaffected. Oxidative bursts were not modified by any of the sub-MICs. The knowledge that these sub-MICs are still effective in increasing bacteria killing, correlated with the pharmacokinetic curve of a common single dose of cefodizime 1 g i.m., showed that the killing effects of sub-MICs may last for as long as 12 h after the activity of the MIC value. This integrated information extends our knowledge of the ultimate efficacy of an antibiotic and provides further information for optimizing scheduling.

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In vitro and in vivo Enhancement of Bactericidal Activity of Phagocytes against <i>Klebsiella pneumoniae </i>treated with Subminimal Inhibitory Concentrations of Cefodizime

Cited by 5 publications

References 23 publications

Influence of Cefodizime on Pulmonary Inflammatory Response to Heat-Killed Klebsiella pneumoniae in Mice

Influence of Cefodizime on Pulmonary Inflammatory Response to Heat-Killed Klebsiella pneumoniae in Mice

Dynamic interactions between cephalexin and macrophages on different Staphylococcus aureus inoculum sizes: a tripartite in vitro model

Influence of Sub-Minimum Inhibitory Concentrations of Cefodizime on the Phagocytosis, Intracellular Killing and Oxidative Bursts of Human Polymorphonuclear Leukocytes

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